Tyrosine phosphorylation in human neutrophil

Gómez‐Cambronero, Julian; Huang, Chi‐Kuang; Bonak, Valerie A.; Wang, Ellen; Casnellie, John E.; Shiraishi, T.; Sha'afi, R.I.

doi:10.1016/0006-291x(89)90841-3

Cited by 123 publications

(53 citation statements)

References 18 publications

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“…While much is known about the coupling of G proteins to phospholipase C, the initial steps involved in the initiation of the tyrosine phosphorylation cascade(s) upon engagement of GPCRs remain, for the most part, undetermined. This lack of knowledge contrasts with the documented importance of tyrosine phosphorylation events in the initiation and/or regulation of several neutrophil functions established using correlative, pharmacological (7)(8)(9)(10)(11), and genetic approaches (12)(13)(14)(15) .…”

mentioning

confidence: 94%

Chemotactic Factor-Induced Recruitment and Activation of Tec Family Kinases in Human Neutrophils. II. Effects of LFM-A13, a Specific Btk Inhibitor

Gilbert

Levasseur²,

Desaulniers³

et al. 2003

The Journal of Immunology

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Tyrosine phosphorylation events play major roles in the initiation and regulation of several functional responses of human neutrophils stimulated by chemotactic factors such as the bacterially derived tripeptide formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). However, the links between the G protein-coupled receptors, the activation of the tyrosine kinases, and the initiation of neutrophil functional responses remain unclear. In the present study we assessed the effects of a Btk inhibitor, leflunomide metabolite analog (LFM-A13), on neutrophils. LFM-A13 decreased the tyrosine phosphorylation induced by fMet-Leu-Phe and inhibited the production of superoxide anions and the stimulation of adhesion, chemotaxis, and phospholipase D activity. We observed a decreased accumulation of phosphatidylinositol-3,4,5-trisphosphate in response to fMet-Leu-Phe in LFM-A13-pretreated cells even though the inhibitor had no direct effect on the lipid kinase activity of the p110γ or p85/p110 phosphatidylinositol 3-kinases or on the activation of p110γ by fMet-Leu-Phe. The phosphorylation of Akt and of extracellular signal-regulated kinases 1/2 and p38 were similarly inhibited by LFM-A13. LFM-A13 also negatively affected the translocation of Rac-2, RhoA, ADP ribosylation factor-1, Tec, Bmx, and Btk induced by fMet-Leu-Phe. The results of this study provide evidence for an involvement of Btk and possibly other Tec kinase family members in the regulation of the functional responsiveness of human neutrophils and link these events, in part at least, to the modulation of levels of phosphatidylinositol-3,4,5-trisphosphate.

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confidence: 94%

Chemotactic Factor-Induced Recruitment and Activation of Tec Family Kinases in Human Neutrophils. II. Effects of LFM-A13, a Specific Btk Inhibitor

Gilbert

Levasseur²,

Desaulniers³

et al. 2003

The Journal of Immunology

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“…Amplified products of P2X [1][2][3][4][5][6][7] were observed in appropriate amounts when homogenized rat brain was used as the positive control for RT-PCR (Fig. 7: A, B).…”

Section: Identification Of Purinoceptor Mrna In Rat Neutrophils By Rtmentioning

confidence: 96%

“…A bacterial peptide, N-formyl-methionyl-leucylphenylalanine (fMLP), identified as a potent leukocyte chemoattractant, binds to receptors on the neutrophil outer membrane, thereby activating these cells through a G-protein-coupled pathway (6,7). ATP and adenosine modulate neutrophil functions, including chemotaxis (8,9).…”

Section: Introductionmentioning

confidence: 99%

P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils

et al. 2012

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Abstract. ATP and hydrolysis products of ATP like adenosine regulate the chemotaxis of neutrophils by activating purinoceptors and adenosine receptors. The present study was designed to examine exogenous ATP, activation of purinoceptors, and activation of A 3 adenosine receptor as key steps in the signal cascades that control cell orientation and migration of rat neutrophils. One or more of those steps might be potential therapeutic targets for treatment of inflammatory diseases. The chemotaxis of rat neutrophils was stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and measured with an EZ-TAXIScan apparatus. The effects of apyrase, exogenous ATP, suramin (P2X and P2Y blocker), PPADS (a P2X blocker), TNP-ATP (P2X 1 and P2X 3 antagonist), and Reactive Blue 2 (a P2Y blocker) on the chemotactic response were also investigated. Rat neutrophil chemotaxis was significantly suppressed by apyrase. fMLP induced rat neutrophil chemotaxis was potentiated by ATP, blocked by suramin, not affected by PPADS or TNP-ATP, and significantly inhibited by RB-2. Western blotting showed that A 3 , P2Y 2 , and P2Y 11 were expressed in rat neutrophils. The chemotactic response of rat neutrophils to fMLP stimulation is potentiated by ATP via P2Y 11 purinoceptors but not P2X purinoceptors or A 3 adenosine receptor, and that the response plays a critical role in host defense and pathogenicity.[Supplementary Movies: available only at http://dx

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“…The GTP-Ga and the free Gbg subunit interact with their respective effector proteins that further amplify the signal. GPCR activation triggers rapid protein tyrosine phosphorylation in neutrophils (8,9), and treatment with inhibitors of tyrosine kinases blocks neutrophil responses to chemoattractants (10,11). Among cytosolic tyrosine kinases, members of the Src family have been implicated in fMLF-mediated signal transduction (12)(13)(14).…”

mentioning

confidence: 99%

The 3BP2 Adapter Protein Is Required for Chemoattractant-Mediated Neutrophil Activation

Chen

Dimitriou

Milne

et al. 2012

The Journal of Immunology

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3BP2 is a pleckstrin homology and Src homology 2 domain-containing adapter protein mutated in cherubism, a rare autosomal-dominant human bone disorder. Previously, we have demonstrated a functional role for 3BP2 in peripheral B cell development and in peritoneal B1 and splenic marginal zone B cell-mediated Ab responses. In this study, we show that 3BP2 is required for G protein-coupled receptor-mediated neutrophil functions. Neutrophils derived from 3BP2-deficient (Sh3bp2−/−) mice failed to polarize their actin cytoskeleton or migrate in response to a gradient of chemotactic peptide, fMLF. Sh3bp2−/− neutrophils failed to adhere, crawl, and emigrate out of the vasculature in response to fMLF superfusion. 3BP2 is required for optimal activation of Src family kinases, small GTPase Rac2, neutrophil superoxide anion production, and for Listeria monocytogenes bacterial clearance in vivo. The functional defects observed in Sh3bp2−/− neutrophils may partially be explained by the failure to fully activate Vav1 guanine nucleotide exchange factor and properly localize P-Rex1 guanine nucleotide exchange factor at the leading edge of migrating cells. Our results reveal an obligate requirement for the adapter protein 3BP2 in G protein-coupled receptor-mediated neutrophil function.

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Tyrosine phosphorylation in human neutrophil

Cited by 123 publications

References 18 publications

Chemotactic Factor-Induced Recruitment and Activation of Tec Family Kinases in Human Neutrophils. II. Effects of LFM-A13, a Specific Btk Inhibitor

Chemotactic Factor-Induced Recruitment and Activation of Tec Family Kinases in Human Neutrophils. II. Effects of LFM-A13, a Specific Btk Inhibitor

P2Y11 Purinoceptor Mediates the ATP-Enhanced Chemotactic Response of Rat Neutrophils

The 3BP2 Adapter Protein Is Required for Chemoattractant-Mediated Neutrophil Activation

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